Insulin gene is a target in activin receptor-like kinase 7 signaling pathway in pancreatic beta-cells.
Activins regulate pancreatic development, differentiation and insulin secretion. Activin receptor-like kinase 7 (ALK7) has been identified as a receptor for Nodal and Activin AB and B, and is expressed in pancreatic islets and beta-cell lines. In this study, human insulin promoter was activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1 (PDX-1) in the ALK7 pathway. A conserved Smad binding element was related to the promoter activation. Phosphorylated Smad2/Smad3 and PDX-1 were bound to insulin gene with Nodal and Activin AB, and the phosphorylated Smad2/Smad3 interacted with PDX-1. These results indicate that one of the direct target genes of Nodal and Activin AB signals is the insulin gene in pancreatic beta-cells and that PDX-1 is directly involved in the ALK7-Smad pathway.
Watanabe
Rie
R
Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. riewata@metab.kuhp.kyoto-u.ac.jp
Shen
Zhen-Ping
ZP
Tsuda
Kinsuke
K
Yamada
Yuichiro
Y
D030201:Activin Receptors, Type I / Q000378:metabolism*; D028341:Activins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004285:Dogs; D006168:Guinea Pigs; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D055457:Nodal Protein / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D016415:Sequence Alignment; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation
D018398:Homeodomain Proteins; D007328:Insulin; C526007:NODAL protein, human; D055457:Nodal Protein; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators; C422405:activin A; C044147:activin B; C084010:pancreatic and duodenal homeobox 1 protein; D028341:Activins; D019869:Phosphatidylinositol 3-Kinases; C424205:ACVR1C protein, human; D030201:Activin Receptors, Type I